European Journal of Cardiovascular Medicine

Cardiac arrest is one of the most frequent mortality cause and neurological morbidity all over the world. Even with current improvements in cardiopulmonary resuscitation and post-resources care, survivors encounter severe cerebral injuries as a result of reperfusion injury and cerebral hypoxia. [1,2,3]. This seems to be true even in the case of post-cardiac arrest syndrome, especially hypoxia-ischemic brain injury, which remains a mostly central factor in dictating long-term functional recovery. [2,4]

Targeted temperature management (TTM) has been a standard of care mediation  to prevent neurologic injury in comatose patients who survive cardiac arrest.[1,5] The recommendations of care allow a target temperature of 32-36 degrees Celsius to be maintained in eligible comatose patients inside an intensive care unit (ICU) after they have had a successful resuscitation (return of spontaneous circulation, ROSC).[5,6] TTM routinely necessitates the use of sedation to alleviate shivering and artificial respiration (mechanical vent Nevertheless, the question of what type of sedation and to what degree it should be is a debatable issue and it is under current research. [8,9,7]

The Richmond Agitation Sedation Scale (RASS) is usually used to measure the depth of sedation. It has been found that this scale can be used to predict brain improvement.  [10,11,12]. To achieve comfort and decrease metabolic need, deep sedation (RASS -4 to -5) may be widely used, however there is evidence, building up, associating deeper levels of sedation with risks of longer ventilator, delirium, and death in numerous critically ill populations. [13,14]. Notably, recent retrospective studies postulated that lighter sedation (RASS -4) in TTM was not related to higher rates of adverse effects and was possibly related with better neurologic values and short-term survival rate of post-cardiac arrest patients. [10, 15]

One of the inherent problems is that sedation that is too deeply can impede early neurological assessment and delay detection of improvement or adverse effects. [9,16] In addition, unrecognized residual sedative can confound prognostication with even assassinating potentially crucial decisions to withdraw care.[17] In contrast, ineffective sedation may contribute to an agitated state, higher cerebral metabolic rates, and a risk of secondary brain damage. [1,8,6] The issue of individualized and evidence-based sedation approaches in the post-cardiac arrest patient is, thereby, gaining recognition. [7,8]

Although sedation is widely used in TTM, it has been pointed out that, unfortunately, large-scale studies prospectively investigating the effect of sedation level on brain results after cardiac arrest are not known. [1,3,8] Observational data and post hoc analysis indeed suggest an improved outcome with lighter sedation, yet it is necessary to have robust data defining and confirming causation and to guide the clinical practice thereafter. [10,15] This study aims to evaluate the impact of sedation depth on neurological outcomes in post-cardiac arrest ICU patients undergoing TTM, addressing a critical gap in contemporary critical care.

Cardiac arrest is one of the most frequent mortality cause and neurological morbidity all over the world. Even with current improvements in cardiopulmonary resuscitation and post-resources care, survivors encounter severe cerebral injuries as a result of reperfusion injury and cerebral hypoxia. [1,2,3]. This seems to be true even in the case of post-cardiac arrest syndrome, especially hypoxia-ischemic brain injury, which remains a mostly central factor in dictating long-term functional recovery. [2,4]

Targeted temperature management (TTM) has been a standard of care mediation  to prevent neurologic injury in comatose patients who survive cardiac arrest.[1,5] The recommendations of care allow a target temperature of 32-36 degrees Celsius to be maintained in eligible comatose patients inside an intensive care unit (ICU) after they have had a successful resuscitation (return of spontaneous circulation, ROSC).[5,6] TTM routinely necessitates the use of sedation to alleviate shivering and artificial respiration (mechanical vent Nevertheless, the question of what type of sedation and to what degree it should be is a debatable issue and it is under current research. [8,9,7]

The Richmond Agitation Sedation Scale (RASS) is usually used to measure the depth of sedation. It has been found that this scale can be used to predict brain improvement.  [10,11,12]. To achieve comfort and decrease metabolic need, deep sedation (RASS -4 to -5) may be widely used, however there is evidence, building up, associating deeper levels of sedation with risks of longer ventilator, delirium, and death in numerous critically ill populations. [13,14]. Notably, recent retrospective studies postulated that lighter sedation (RASS -4) in TTM was not related to higher rates of adverse effects and was possibly related with better neurologic values and short-term survival rate of post-cardiac arrest patients. [10, 15]

One of the inherent problems is that sedation that is too deeply can impede early neurological assessment and delay detection of improvement or adverse effects. [9,16] In addition, unrecognized residual sedative can confound prognostication with even assassinating potentially crucial decisions to withdraw care.[17] In contrast, ineffective sedation may contribute to an agitated state, higher cerebral metabolic rates, and a risk of secondary brain damage. [1,8,6] The issue of individualized and evidence-based sedation approaches in the post-cardiac arrest patient is, thereby, gaining recognition. [7,8]

Although sedation is widely used in TTM, it has been pointed out that, unfortunately, large-scale studies prospectively investigating the effect of sedation level on brain results after cardiac arrest are not known. [1,3,8] Observational data and post hoc analysis indeed suggest an improved outcome with lighter sedation, yet it is necessary to have robust data defining and confirming causation and to guide the clinical practice thereafter. [10,15] This study aims to evaluate the impact of sedation depth on neurological outcomes in post-cardiac arrest ICU patients undergoing TTM, addressing a critical gap in contemporary critical care.

The study comprised of 150 post-cardiac arrest patients in which targeted temperature management (TTM) was done. Out of them, 55 patients belonged to the lighter sedation group (mean RASS -4) and 95 patients were included in the deeper sedation group (mean RASS -5). Baseline characteristics for the two groups were mostly the same. There were no statistically significant differences in age, sex distribution, initial cardiac rate, or time to ROSC (Table 1).

Neurological Outcomes

The proportion of patients exhibiting favorable neurological outcomes (Cerebral Performance Category (CPC) score 12) was significantly greater in the lighter sedation cohort (49.1%) than in the deeper sedation cohort (34.7%; p = 0.048) (Table 2). This disparity is pictorially illustrated in Figure1, which shows the distribution of the positive neurological outcomes between the degrees of sedation.

Survival Outcomes

There was no statistically significant difference in the ICU survival between the two groups (70.9% vs. 69.5%, p = 0.85). But 30-day all-cause mortality was significantly reduced in the lighter sedation group (29.1 %) than the deeper sedation group (42.1 %) (p = 0.041) (Table 2). This survival advantage is further demonstrated when the Kaplan Meier survival curve analysis (Figure 2) depicts a better 30-days survival chance in the lighter sedation group. The confidence interval of the difference between the two survival curves was reported as 0.041 which showed a statistically significant difference between the two survival curves.

Multivariate Analysis

Multivariable logistic regression analysis indicated that the neurologic outcomes of lighter sedation (RASS -4) were independently associated with an enhanced neurologic outcome (unadjusted OR 2.07; 95% CI: 1.01 4.27; p = 0.045) despite controlling confounding by age, initial rhythm, and time to ROSC (Table 3). The age and the time to ROSC were also relevant predictive factors of neurological recovery.

Table 1: Baseline Characteristics of ICU Patients Post-Cardiac Arrest

Comparison of demographic and baseline clinical characteristics between the lighter and deeper sedation groups.

Table 2: Clinical Outcomes According to Sedation Depth

Neurological and survival outcomes among patients with lighter versus deeper sedation during targeted temperature management.

Table 3: Multivariate Logistic Regression Analysis for Favorable Neurological Outcome

Multivariable regression analysis identifying predictors of favorable neurological outcome (CPC 1–2) at ICU discharge.

Figure 1: Proportion of Patients Achieving Favorable Neurological Outcome (CPC 1–2)

Bar graph showing the percentage of patients in each sedation group who achieved a favorable neurological outcome at ICU discharge.

Figure 2: Kaplan-Meier Curve for 30-Day Survival Stratified by Sedation Depth

Kaplan–Meier survival analysis comparing 30-day all-cause mortality between lighter and deeper sedation groups.

The retrospective observational study has demonstrated that light sedation (mean RASS -4) during the first 48 hours of targeted temperature management (TTM) in patients proved to have a significant correlation with better neurological outcome and lower 30-day mortality. These conclusions are agreeable with the emerging evidence that supports the idea of reduced sedation in the neurocritical care group. Our findings are in line with those of Ceric et al. (2025a) [21], who pointed out that ideal sedation plans that are patient-centered including those with acute brain injury are of great importance to patients with post-cardiac arrest status. The SED-CARE trial protocol [17] upholds the clinical equipoise of the intensity of sedation comparing continuous deep sedation with minimal sedation and advocates the relevance of outcome-based approach to sedation therapy. The present research grants initial real-life evidence of this trend.

A scientific statement released by the American Heart Association and the Neurocritical Care Society, authored by Hirsch et al. [18] also indicated that deep sedation may slow neuroprognostication and therefore resulted in premature termination of life support because of inaccurate neurological recovery. Our research supports this issue, with more sedated patients (RASS -5) having independently worse outcomes about neurological condition, regardless of some critical factors such as age and time to ROSC. Also, Pelentritou et al. [19] proved that sedative depth has a great impact on the prediction of coma outcomes based on EEG recordings. Our research contributes to this by demonstrating that lighter sedation potentially supports earlier and more precise neurological evaluation with less false negative when making prognosis. Geller et al. [20] and Ceric et al. (2025b) [21] emphasized the institutional differences in the practice of sedation and shivering management during TTM, which indicates that the discrepant protocols may not only impact the outcome. Our investigation did not reveal a disparity in ICU survival between the reduced sedation and conventional ICU treatment groups; rather, a shorter-term (30-day) survival benefit in the lighter sedation group, which indicates that sedation depth is only associated with long-term outcome, as opposed to acute survival in the ICU.

Further insignificant relationships are also supported by Roginski et al. [22], who observed that the depth of sedation during transport and hospitalization with patients was linked to the neurological outcome. The same way, the adoption of predictive models suggested by Kim et al. [23] can be improved by incorporating the depth of sedation as a reversible prognostic variable. On a wider sense, the risks of using volatile anaesthetics to assist in sedation have been investigated and it could provide some neuroprotective effects [24]. Nonetheless, they are not extensively deployed since they are not feasible. Conversely, Shen et al. [25] as well as the recent clinical trials have shown that dexmedetomidine projects neuroprotective effects in animal models, and it can be used to enhance the quality of sleep and recovery process after cardiac surgery. Moreover, objective measures of the sedation effect based on early neuroprognostication tools (Patient State Index or suppression ratio) [26][27] are also available and support the idea that deep sedation should be avoided because it may obscure assessment of sedation effects.[28][29] The same need is also acute in paediatrics where Slovis et al. [30] indicate that neuromonitoring following cardiac arrest is also important in charting the cerebral damage progression.

Our study’s results also resonate with those of Hawkins et al. [31], who termed sedation as a “chilling confounder” to TTM—emphasizing that sedative agents can mask underlying cerebral recovery or deterioration. Leadbeater et al. [32] found that outcomes after cardiac arrest varied depending on whether fever prevention or active TTM was applied—again underlining that the sedation method employed can critically shape patient trajectories.

Finally, the real-world challenges of sedative choice in pre-hospital and emergency settings, such as those outlined by Jansen et al. [29], may have downstream effects on in-hospital sedation practices and neurological prognoses. The variation in pre-hospital midazolam use observed in their multicentre study suggests the need for sedation standardization across the continuum of care. Collectively, our data substantiate the concept that less sedation during the first post-resuscitation phase correlates with enhanced neurological outcomes and survival rates. These results are consistent with a growing body of literature [16–32] and reinforce the call for individualized, neuroprotective sedation strategies in patients undergoing TTM after cardiac arrest. Prospective trials such as SED-CARE will be pivotal in confirming these associations and guiding future ICU sedation protocols.

This study of post-cardiac arrest patients receiving targeted temperature management (TTM) found that lighter sedation (RASS -4) in the initial 48 hours of ICU admission was independently linked to markedly improved neurological outcomes and reduced 30-day all-cause mortality relative to deeper sedation (RASS -5). These findings highlight the potential clinical importance of individualized sedation strategies in improving neuroprognostication and recovery after cardiac arrest. While ICU survival did not differ significantly, the improvement in neurologic recovery and medium-term survival emphasizes the role of sedation depth as a modifiable factor in post-resuscitation care. Prospective, multicenter randomized trials are warranted to validate these findings and inform future sedation protocols in this high-risk population. 

This study of post-cardiac arrest patients receiving targeted temperature management (TTM) found that lighter sedation (RASS -4) in the initial 48 hours of ICU admission was independently linked to markedly improved neurological outcomes and reduced 30-day all-cause mortality relative to deeper sedation (RASS -5). These findings highlight the potential clinical importance of individualized sedation strategies in improving neuroprognostication and recovery after cardiac arrest. While ICU survival did not differ significantly, the improvement in neurologic recovery and medium-term survival emphasizes the role of sedation depth as a modifiable factor in post-resuscitation care. Prospective, multicenter randomized trials are warranted to validate these findings and inform future sedation protocols in this high-risk population.